Inclusion Criteria  Subjects with biopsy-proven adenocarcinoma of the pancreas Pancreatic protocol helical CT scan demonstrating absence of venous or arterial involvement, consistent with NCCN guidelines for resectable disease ECOG performance status ≤ 1 No active second malignancy except for basal cell carcinoma of the skin  Normal renal, hepatic, and hematologic function at the time of enrollment as evidenced by:  Serum creatinine level ≤1.5 the upper limits of normal Serum total bilirubin level ≤1.5 X ULN White blood cell count ≥ 3.5x109/ml per ml and platelet count ≥ 100x109 per ml For subjects with obstructive jaundice, the biliary tract must be drained with a temporary plastic or a short permanent metallic biliary stent Ability to understand and the willingness to sign a written informed consent document.  Exclusion Criteria  Subjects deemed surgically unresectable or subjects unwilling to undergo surgical resection. Subjects who have received chemotherapy within 12 months prior to study entry. Subjects who are found to have loss-of-function mutations in DPYD or UGTA1 by Oneome pharmacogenomic testing, resulting in increased risk of mFOLFIRINOX toxicity. DPYD mutations have been noted in 5% of the overall population. Homozygous UGT1A1 mutations have been noted in 10% of North Americans. Prior use of radiotherapy or investigational agents for pancreatic cancer. Any evidence of metastasis to distant organs (liver, lung, peritoneum). Cross sectional imaging suggesting portal vein, superior mesenteric artery, hepatic artery involvement that would make the patient borderline resectable or locally advanced Symptomatic or endoscopic evidence of gastric outlet obstruction. Concurrent malignancies with evidence of active or measurable disease except basal cell carcinoma of the skin. Inability to adhere to study and/or follow-up procedures. History of allergic reactions or hypersensitivity to the study drugs (chloroquine, hydroxychloroquine, 5-Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan). Other concurrent experimental therapy. The effects of HCQ, and mFOLFIRINOX on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. All females of childbearing potential must have a blood test or urine study within two weeks prior to registration to rule out pregnancy. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. If a man impregnates a woman while participating in this study, he should inform his treating physician immediately as well. Because patients with immune deficiency are at increased risk of lethal infections when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded from the study. For patients receiving combination anti-retroviral therapy, the potential impact of pharmacokinetic interactions with HCQ and mFOLFIRINOX is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future. Due to the risk of disease exacerbation, patients with porphyria are ineligible. Patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist who agrees to monitor the patient for exacerbations. Patients requiring the use of enzyme-inducing anti-epileptic medication that includes: phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine are excluded. Patients with previously documented macular degeneration or diabetic retinopathy are excluded. Baseline EKG with QTc >470 msec (including subjects on medication). Subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basis.