Prespecified exploratory genomic and transcriptomic profiling of tumor tissues and circulating tumor DNA from patients with BRAF-V600E-mutant metastatic colorectal cancer who participated in the phase 3 BEACON CRC trial identifies biomarkers of response and mechanisms of acquired resistance to treatment with the BRAF inhibitor encorafenib plus the anti-EGFR antibody cetuximab, with or without the MEK inhibitor binimetinib. Here, BRAF is linked to metastatic colorectal cancer.