Background: Colorectal cancer patients with brain metastases experience poor outcomes; however treatment strategies are understudied. In this study, we investigated the impact of different treatments for colorectal cancer patients with brain metastases. Methods: We identified stage 4 colorectal adenocarcinoma patients with brain metastasis using the National Cancer Database diagnosed between 2010 and 2015. Patients with unknown survival data, other histologies, and multiple primary sites were excluded. Patients with and without brain metastasis were compared using the Chi-square test. Kaplan-Meier method was performed to calculate univariable overall survival (OS). We used the Cox regression model for multivariable analysis after adjusting by age, race/ethnicity, comorbidity score, surgery, chemotherapy, and radiotherapy. Results: Among 75,901 patients with stage 4 colorectal adenocarcinoma, 1.6% had brain metastasis. Patients with brain metastasis were more likely to have bone (23% vs. 5%, p < 0.001) and lung metastasis (52% vs. 21%, p < 0.001), but less likely to have liver metastasis (56% vs. 72%, p < 0.001) compared to patients without brain metastasis. Patients with brain metastasis had higher KRAS mutation rate (54% vs. 43%, p < 0.001). Patients with brain metastasis were more likely to be age ≥ 50 years (85% vs. 83%, p = 0.01), white race (76% vs. 71%, p = 0.001), and receive radiotherapy (63% vs. 12%, p < 0.001). Total 26.4% of patients with brain metastasis underwent metastasectomy, and those patients had better OS compared to patients with non-metastasectomy (median OS 12 vs. 4 months, p < 0.001). Median OS in all patients with brain metastasis was 5.5 months. Patients with brain metastasis who received multiagent chemotherapy had improved OS compared with patients who received single-agent chemotherapy (mOS 13 vs. 6 months, p < 0.001). Patients with brain metastasis who received brain radiotherapy had better OS (mOS 6.3 vs. 3.7 months, p = 0.005) than those who did not. On multivariable analysis, metastasectomy (HR 0.65 95% CI [0.57-0.75]) and receipt of multiagent chemotherapy (HR 0.68 95% CI [0.54-0.86]) were associated with favorable prognosis, but brain radiotherapy was not (HR 1.04 95% CI [0.91-1.19]). Conclusions: Brain metastases are rare in colorectal cancer but portend poor survival. Lung and bone metastases are found more frequently in these patients. Treatment with metastasectomy or multiagent chemotherapy is associated with improved overall survival.