Background: Colorectal cancer patients with BRAF V600E mutations may be a heterogeneous population with different outcomes. Clinical and molecular pathologic factors related to the prognosis of colorectal cancer need further investigation. Methods: The clinical and pathological information of 206 patients with BRAF V600E mutated colorectal cancer diagnosed in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2014 to 2021 was retrospectively collected. LASSO regression, COX regression and Nomograms were used to develop clinical prognostic models. The differentiation was measured by C-statistic and decision curve analysis, and the predicted variability was evaluated by calibration curve. The prognostic model was externally validated with validation set data from 164 patients pooled from 5 studies. Results: Our clinical prognostic model included three variables: pathological stage, microsatellite status, and primary tumor site. In internal validation, the model had a concordant index of 0.785 (95%CI [0.732-0.839]) and a concordant index of 0.754 (95%CI [0.698-0.810]) using pathological staging. External validation confirmed the robustness of the model with a consistency index of 0.670 (95%CI ([0.617-0.724]) and a consistency index of 0.584 (95%CI [0.546-0.622]) using pathological staging. The application of decision curve analysis in both the training set and the validation set showed that our three-factor clinical prediction model was superior to the pathological staging. The calibration graph drawn based on the prediction and the actual situation is close to the 45° diagonal. Conclusions: By adding microsatellite status and primary tumor site on the basis of pathological stage, we improved the discriminability and prediction accuracy of the model, and successfully established a prognosis model for patients with BRAF V600E mutation of colorectal cancer.