AbstractBackgroundBRAFmutation occurs in 5%–10% of metastatic colorectal cancers (mCRCs). Patients withBRAFmutant mCRC exhibit a specific metastatic pattern and poor prognosis. Survival outcomes are heterogeneous in cases of mCRC with aBRAFmutation. The optimal first‐line therapy is still controversial.MethodsWe retrospectively reviewed the medical records of patients with mCRC between June 2010 and December 2021. Clinicopathologic characteristics, treatment andBRAFmutation testing results were collected. Patients with a BRAF mutation were included. Kaplan–Meier methods and log‐rank tests were used to analyze and compare survival. Cox proportional hazards regression was used to establish the predictive nomogram model.ResultsOf the 4475 mCRC, 261 have aBRAFmutation, including 240 V600E and 21 non‐V600E mutants. The median overall survival (OS) was 18.2 months in theBRAFV600E mutant group versus 38.0 months in the non‐V600E mutant group (p= 0.022). ECOG score, tumor differentiation, liver metastasis, bone metastasis and primary tumor resection were independent prognostic factors for the OS ofBRAFV600E mutant mCRC. A nomogram model was established using these factors. The median OS was 39.3 m, 18.2 m and 10.7 m for the low‐risk, intermediate‐risk and high‐risk groups defined by this model, respectively (p< 0.0001). Patients who received first‐line triplet chemotherapy ± bevacizumab had comparable progression free survival (PFS) and OS compared with those treated with doublets ± bevacizumab.ConclusionBRAFV600E mutant mCRCs exhibit unfavorable and heterogeneous prognosis. The first‐line intensive chemotherapy did not confer a marked impact on the PFS and OS.