Metastatic colorectal cancer with the BRAF V600E mutation has a poor prognosis. An open-label, phase III trial enrolled 665 patients who had disease progression after previous regimens. Patients were randomly assigned to receive encorafenib, binimetinib and cetuximab (triple therapy), encorafenib and cetuximab (double therapy) or cetuximab and irinotecan or cetuximab and FOLFIRI (folinic acid, fluorouracil and irinotecan) (control group). Median overall survival was 9.0 months in the triple-therapy group, 8.4 months in the double-therapy group and 5.4 months in the control group. Response rate was 26% in the triple-therapy group and 2% in the control group.