Background: Patients with metastatic colorectal cancer (mCRC) and mutations in BRAF V600E (mutBRAF) or KRAS (mutKRAS) have a worse prognosis after liver or lung surgery/ablation, whereas the impact of microsatellite instability (MSI-H) has not been well studied. Few patients with mutBRAF receive liver or lung surgery (1-4%), whereas mutBRAF is present in 5-12% of mCRC trial patients and in up to 20% of the general mCRC population. The frequency and prognostic role of mutBRAF, mutKRAS and MSI has not been well studied after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases from colorectal cancer. Methods: The Norwegian Radium Hospital is the only center offering CRS and HIPEC in Norway. From 2004 to 2015 257 patients with histology proven peritoneal metastasis from colorectal cancer, appendiceal cancer excluded, was consecutively enrolled. Molecular analyses of KRAS, BRAF and MSS/MSI in mutBRAF were done. Fourteen patients were excluded due to missing tumour blocks (7), unsuccessful analysis (4) and other malignant disease (1). Results: 180 of 243 patients obtained complete cytoreductive surgery and received HIPEC for 90 minutes with Mitomycin C (45-70mg). Median survival for the 180 patients was 47 months and 5-year survival rate 40.1%. Median disease-free survival was 10 months. mutBRAF was found in 23.4% of cases, mutKRAS 35.1% and double-wild type 41.5%. mutBRAF with MSS was found in 16.4%, mutBRAF with MSI-H in 7.0%. 3-year disease free survival (DFS) and median overall survival (OS) was 38.9% and 59 months with mutBRAF with MSI-H, significantly higher compared to 24.2% and 30 months in patients with double wild type, 13.2 % and 41 months in mutKRAS and 17.9% and 22 months in mutBRAF with MSS. Conclusions: A surprisingly high frequency of mutBRAF was seen in mCRC patients after CRS and HIPEC for peritoneal metastatic disease. Patients with mutBRAF and MSI-H had a significantly better DFS and OS after CRS and HIPEC. DFS for patients with mutBRAF and MSS was numerically lower but not statistically different from patients with mutKRAS or double wild type.