Background: BRAF (v-raf murine sarcoma viral oncogene homolog B1) V600E mutant colorectal cancer is associated with short survival. Recently, clinical trials have been conducted to improve outcomes of second or later lines of chemotherapy. However, there is a paucity of reference data pertaining to outcomes of second-line chemotherapy and prognostic factors that are relevant only to BRAF mutant patients. Patients and methods: We retrospectively reviewed metastatic colorectal cancer patients with BRAF V600E mutation who underwent second-line chemotherapy between January 2007 and March 2017. We evaluated treatment outcomes and performed prognostic analyses. Results: A total of 52 patients were included. The median progression-free survival and overall survival (OS) were 2.5 [95% confidence interval (CI) = 1.91–4.11] and 6.5 (95% CI = 4.30–9.63) months, respectively. Overall response and disease control rates were 7% and 48%, respectively. All the regimens which elicited a partial response included BRAF inhibitors in combination with anti-epidermal growth factor receptor (EGFR) antibodies. Therefore, the overall response was 0% after exclusion of patients treated with study drugs. Multivariate analysis for OS revealed that the Glasgow Prognostic Score (GPS), elevated lactate dehydrogenase, and poor performance status were independent prognostic factors. In particular, survival curves according to the GPS stratified the patients into distinct risk groups. The median OSs in patients with GPS of 0, 1, and 2 were 9.9, 5.0, and 1.9 months, respectively. Conclusions: Outcomes of second-line chemotherapy for metastatic colorectal cancer patients with BRAF V600E mutation were extremely poor. GPS may be useful in future clinical trials.