Clinical Summary: Design/Population: Cohort 3 of the phase 3 BREAKWATER trial randomized 147 patients with previously untreated, BRAF V600E-mutant metastatic colorectal cancer and ECOG performance status 0–1 to receive encorafenib plus cetuximab and FOLFIRI (EC+FOLFIRI) or standard FOLFIRI-based therapy with or without bevacizumab.