Purpose: Salvage therapy for patients with unresectable colorectal liver metastases that were refractory to oxaliplatin and irinotecan was performed via radioactive microspheres. High doses of radiation were delivered to tumors from permanently implanted 90Y microspheres, delivered through the hepatic arterial vessels. Methods and Materials: Patients from 7 institutions were selected for treatment after screening-defined vascular access to all the tumors, and imaging-confirmed microspheres would be implanted only in the liver tumors. All patients were followed with laboratory and imaging studies at regular intervals until death. Toxicities, both acute and late, were recorded, and actuarial survival determined. Results: A total of 208 patients were treated from April 2002 to April 2005. Median follow-up of the 129 men and 79 women is 13 months (range, 1–42 months). Median survival is 10.5 months for responders but only 4.5 months in nonresponders. No treatment-related procedure deaths or radiation-related venoocclusive liver failures were found. Computed tomography partial response was 35%; positron emission tomography response of 91% and reduction in carcinoembryonic antigen of 70% were achieved. Conclusions: In this group of heavily pretreated patients, radioactive microspheres produced an encouraging median survival, with acceptable toxicity, and a significant objective response rate, which suggests that further investigation of this approach is warranted.