Inclusion Criteria for Molecular Prescreening:  The following inclusion criteria must be met for a participant to be eligible to undergo molecular tumor prescreening:  Chinese male or female participant with age ≥18 years at the time of informed consent. Histologically- or cytologically-confirmed colorectal cancer (CRC) that is metastatic. Eligible to receive cetuximab per Chinese approved label with regard to tumor Rat Sarcoma Viral Oncogene Homologue (RAS) mutation status (i.e. approved for Rat Sarcoma Viral Oncogene Homologue Wild Type(RAS wt) status). Able to provide a sufficient amount of representative tumor specimen for central prospective laboratory testing of B-RAF Proto-oncogene, Serine/threonine Kinase (BRAF) mutation status and also retrospective RAS wt status and Microsatellite Instability (MSI) testing.  Inclusion Criteria for Treatment Period:  The following inclusion criteria must be met for a participant to be eligible for this study:  Chinese male or female participant with age ≥18 years at time of informed consent. Histologically or cytologically confirmed CRC that is metastatic and unresectable at time of study entry (i.e. not suitable for complete surgical resection at screening). Presence of a BRAF V600E mutation in tumor tissue previously determined by a local assay at any time before screening or by the central laboratory.  NOTE: Other protocol defined Inclusion criteria may apply  Exclusion Criteria for Molecular Prescreening:  Participants meeting any of the following criteria are not eligible to undergo molecular tumor prescreening:  Prior anti-Epidermal Growth Factor Receptor (anti-EGFR) treatment More than two prior regimens in the metastatic setting. Known contraindication to receive cetuximab or irinotecan at the planned dose according to the most recent cetuximab and irinotecan local label. Known history of Gilbert's syndrome or is known to have any of the following genotypes: uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*6/*6, UGT1A1*28/*28 or UGT1A1*6/*28. Leptomeningeal disease.  Exclusion Criteria for Treatment Period:  Prior treatment with any Proto oncogene Serine/threonine-Protein Kinase (RAF) inhibitor, cetuximab, panitumumab or other EGFR inhibitors. Symptomatic brain metastasis. Leptomeningeal disease. Use of any herbal medications/supplements or any medications or foods that are moderate or strong inhibitors or inducers of cytochrome P450 (CYP)3A4/5 ≤1 week before the start of study intervention. Known history of acute or chronic pancreatitis within 6 months before the start of study intervention.  NOTE: Other protocol defined Exclusion criteria may apply