Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

Key Inclusion Criteria: * Age ≥ 18 years at time of informed consent * Histologically- or cytologically-confirmed CRC that is metastatic * Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory * Progression of disease after 1 or 2 prior regimens in the metastatic setting * Evidence of measurable or evaluable non-measurable disease per RECIST, v1.1 * Adequate bone marrow, cardiac, kidney and liver function * Able to take oral medications * Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of childbearing potential * Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up Key Exclusion Criteria: * Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab, panitumumab or other epidermal growth factor receptor (EGFR) inhibitors * Prior irinotecan hypersensitivity or toxicity that would suggest an inability to tolerate irinotecan 180 mg/m2 every 2 weeks * Symptomatic brain metastasis or leptomeningeal disease * History or current evidence of retinal vein occlusion or current risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes) * Known history of acute or chronic pancreatitis * Hist…