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Brain metastases (BMs) from colorectal cancer (CRC) are unusual; however, an increase in incidence has been reported. The evidence available on the subject is scarce, and a better understanding is warranted. We aimed to characterize the epidemiology and the outcomes of patients with BMs from CRC.A cohort of patients with BMs from CRC was retrospectively evaluated. Patients were treated in a single center between May 2008 and April 2019. BMs were confirmed by brain computed tomography or magnetic resonance imaging.A total of 247 consecutive patients were evaluated. Most patients had a left-sided primary tumor (193, 78%) and at least two extra-cranial metastatic sites (194, 78%). Ninety-six patients (39%) were RAS wild-type; 68 patients (27%) were RAS mutated; and 83 patients (34%) were not characterized. Median time from the initial diagnosis to BMs was 27.6 months (interquartile range, 13.1-46.9). Regarding local therapy, 43 patients (17.4%) were treated with BM surgery alone, 76 patients (30.8%) with radiotherapy (RT) alone, and 58 patients (23.5%) with both surgery and RT. Median overall survival (OS) was 2.9 months (95% confidence interval [CI], 2.2-3.5). Six-month and 1-year OS rates were 29% (95% CI, 23-25) and 13.5% (95% CI, 9.2-18.6), respectively. In a multivariable analysis, BM surgery alone (hazard ratio [HR], 0.56; P = .018), RT alone (HR, 0.51; P = .001), and surgery plus RT (HR, 0.27; P.001) were associated with superior OS, whereas Eastern Cooperative Oncology Group Performance Status 3 or 4 (HR, 2.01; P = .009) and male gender (HR, 1.46; P = .012) were negative prognostic factors. RAS status was not associated with OS.BMs occur late during the course of colorectal cancer and are more common in patients with a left-sided primary tumor and a high volume of metastatic disease. BMs from colorectal cancer are still associated with an extremely poor prognosis; however, selected patients may benefit from treatment with surgical resection and radiotherapy.