OBJECTIVE To present data for radioembolization with yttrium-90 ((90)Y) resin microspheres in patients with colorectal cancer liver metastases in whom currently available therapies had failed. METHODS Retrospective review was conducted of case files of patients with colorectal cancer liver metastases in whom chemotherapy had failed, prompting hepatic (90)Y radioembolization administered as a single-session, whole-liver treatment. Imaging and laboratory follow-up results were available for 36 patients. Response and toxicity were assessed by computed tomography/magnetic resonance imaging with the Response Evaluation Criteria in Solid Tumors and the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0. RESULTS Forty-one patients (mean age, 61 years; 30 men) received hepatic (90)Y radioembolization with resin microspheres (mean activity, 1.9 GBq). At a median interval of 2.9 months after radioembolization, partial response, stable disease, and progressive disease were demonstrated in seven, 25, and four patients, respectively. Median overall survival was 10.5 months, with improved survival for patients with a decrease in carcinoembryonic antigen level (19.1 months vs 5.4 months) and imaging response (29.3 months vs 4.3 months; P = .0001). Except for one instance of treatment-associated cholecystitis (grade 4 toxicity) and two gastric ulcers (grade 2 toxicity), no severe toxicities were observed. CONCLUSIONS Hepatic (90)Y radioembolization can be performed with manageable toxicity in patients with colorectal cancer liver metastases whose disease is refractory to chemotherapy. The antitumoral effect is supported by imaging and tumor marker responses. Further investigation is warranted to determine the optimal use of this emerging therapeutic modality.