As most active chemotherapy agents against Wilms tumor are incorporated into upfront therapy, particularly for those patients with high risk for recurrence, novel regimens are needed to treat children with relapsed Wilms tumor. We describe four consecutive patients with multiply relapsed Wilms tumor who were treated with a combination of vincristine, irinotecan, temozolomide, and bevacizumab. Two had a complete response, and two had a partial response to treatment. Hematological toxicity and diarrhea were the main side effects. This regimen has activity in patients with multiply relapsed Wilms tumor without excessive toxicity, and should be evaluated further in this setting. Pediatr Blood Cancer 2014;61:756–759. © 2013 Wiley Periodicals, Inc.