Inclusion Criteria:  Have provided written informed consent prior to any study specific procedures. Age ≥ 18 years. Histologically confirmed diagnosis of stage III or T4N0 stage II colon cancer (located 12 cm from the anal verge by endoscopy and above the peritoneal reflection at surgery) or histologically confirmed diagnosis of locally-advanced resectable rectal cancer (proximal margin located at < 12 cm from the anal verge). Radical surgery for patients with colon cancer or preoperative (chemo)-radiotherapy followed by radical surgery for patients with rectal cancer. Completion of at least 3 months of oxaliplatin-based (CAPOX or FOLFOX) adjuvant chemotherapy (or candidate to oxaliplatin-based adjuvant chemotherapy if post-surgery pre-screening). Availability of the archival FFPE tumor tissue obtained prior to any treatment. Acceptance to undergo all the interventional and exploratory liquid biopsies. Absent MGMT expression by IHC, MGMT promoter methylation by pyrosequencing (> 5%) and MSS by standard assessment. Presence of ctDNA in the liquid biopsies collected at 2-6 weeks after the last dose of standard adjuvant chemotherapy Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Completion of adjuvant chemotherapy for a duration of at least three months. Adequate organ function as defined below: Hematological function indicated by all of the following:  White Blood Cell (WBC) count ≥ 2 x 109/L Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL (patients may have transfusions and/or growth factors to attain adequate Hb).  - Liver function indicated by all of the following: Total bilirubin < 1.5 x upper limit of normal (ULN) Aspartate transaminase (AST) and alanine aminotransferase (ALT) < 3 x ULN Alkaline phosphatase (ALP) < 2 x ULN.  - Renal function indicated by all of the following: Serum creatinine < 1.5 x ULN or calculated creatinine clearance > 40 ml/min.  - Coagulation indicated by all of the following: INR ≤ 1.5 and aPTT ≤ 1.5 x ULN within 7 days prior to the start of study treatment for patients not receiving anti-coagulation. a. NOTE: The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard of the enrolling institution) and the patient has been on a stable dose of anticoagulants for at least two weeks prior to the start of study treatment.  Carcinoembryonic antigen (CEA) level ≤ 10 ng/ml. No evidence of distant metastases or loco-regional disease by computed tomography scan or magnetic resonance imaging. Male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception). Women of childbearing potential must have a negative blood pregnancy test at the baseline visit and must be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception). For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive.  Exclusion Criteria:  History of another neoplastic disease, unless in remission for ≥ 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Had an incomplete diagnostic colonoscopy and/or polyps removal. Microscopic or macroscopic evidence of residual tumor (R1 or R2 resections). Patients should never have had any evidence of metastatic disease (including presence of tumor cells in the peritoneal lavage). Current or recent treatment with another investigational drug or participation in another investigational study. Inability to swallow pills. Active infection requiring intravenous antibiotics at the start of study treatment. Evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the study medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of study results.  Patient unable to comply with the study protocol owing to psychological, social or geographical reasons.  Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study. Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment. Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to start of study treatment, myocardial infarction ≤ 6 months prior to study enrolment, unstable angina, New York Heart Association (NYHA) Functional Classification Grade II or greater congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment. Known presence of one of the following UGT1A1 1(TA)6/UGT1A1 36(TA)5; UGT1A1 28(TA)7/UGT1A1 37(TA)8 (homozygous genotype). Known presence of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption