Inclusion Criteria:  Age ≥ 18 years. Willing and able to give written informed consent. Have histologically or cytologically confirmed metastatic CRC harboring applicable mutation(s) (e.g., BRAF V600E; KRAS or NRAS mutations) based on an analytically validated assay performed on tumor tissue in a certified testing laboratory. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Adequate bone marrow and organ function. Have ECOG performance status of 0 or 1. Willing to comply with all protocol-required visits, assessments, and procedures. Able to swallow oral medication.  Exclusion Criteria:  Prior therapy with a RAS, MEK, or ERK inhibitor. Depending on which treatment arm the patient is assigned, other therapies could also be prohibitive. Anti-cancer therapy ≤ 21 days or 4 half-lives prior to first dose of study drug, whichever is shorter. Palliative radiation ≤ 7 days prior to first dose of study drug. Symptomatic brain metastasis or leptomeningeal disease. Gastrointestinal conditions that may affect absorption of oral medications Active infection requiring systemic therapy, or history of HIV infection, hepatitis B virus, or hepatitis C virus. History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months prior to first study drug dose. Active, clinically significant interstitial lung disease or pneumonitis. Impaired cardiovascular function or clinically significant cardiovascular disease. History of thromboembolic or cerebrovascular events ≤ 6 months prior to first dose. Major surgery within 28 days of enrollment, or anticipation of major surgery during study treatment. Known intolerance or contraindication to encorafenib, cetuximab, or palbociclib. Pregnant or breastfeeding women. Any evidence of severe or uncontrolled systemic disease or evidence of any other significant clinical disorder or laboratory finding that renders the patient inappropriate to participate in the study.