The purpose of this study was to evaluate the effectiveness of colorectal cancer (CRC) liver metastasis radioembolization with yttrium-90 (Y90), assessing toxicity and survival rates in patients with no response to chemotherapy through our 3-year experience. From February 2005 to January 2008, we treated 41 patients affected by CRC from a cohort of selective internal radiation therapy patients treated at our institution. All patients examined showed disease progression and arrived for our observation with an abdominal CT, a body PET, and a hepatic angiography followed by gastroduodenal artery coiling previously performed by us. We excluded patients with a bilirubin level>1.8 mg/dl and pulmonary shunt>20% but not patients with minor extrahepatic metastases. On treatment day, under fluoroscopic guidance, we implanted a dose of Y90 microspheres calculated on the basis of liver tumoral involvement and the body surface area formula. All patients were discharged the day after treatment. We obtained, according to Response Evaluation Criteria on Solid Tumors, a complete response in 2 patients, a partial response in 17 patients, stable disease in 14 patients, and progressive disease in 8 patients. In all cases, we obtained a carcinoembryonic antigen level decrease, especially in the week 8 evaluation. Technical success rate was 98% and technical effectiveness estimated at 3 months after treatment was 80.5%. Side effects graded by Common Terminology Criteria on Adverse Events were represented by one grade 4 hepatic failure, two grade 2 gastritis, and one grade 2 cholecystitis. The median survival and the progression-free survival calculated by Kaplan-Meier analysis were 354 and 279 days, respectively. In conclusion, according to our 3-year experience, Y90 SIR-Spheres radioembolization is a feasible and safe method to treat CRC liver metastases, with an acceptable level of complications and a good response rate.