Abstract Mantle cell lymphoma (MCL) generally exhibits an aggressive disease course with poor outcomes. Despite inherent radiosensitivity, radiation therapy (RT) is not commonly used for MCL. This study assesses the role of low-dose RT (LDRT) with concurrent chemotherapy in relapsed, multiply refractory MCL. From 2014 through 2018, 19 patients with relapsed, refractory MCL had 98 sites treated with 4 Gy. Median follow-up from initial LDRT was 15.4 months. Patients had received a median 7 courses of chemotherapy since diagnosis, and 58% were ibrutinib-refractory. Of the 98 sites, 76% were refractory to ongoing chemotherapy, and LDRT was delivered with concurrent chemotherapy for 76%. The complete response (CR) rate was 81% at a median 2.7 months post-LDRT. There were no differences in CR despite ibrutinib-refractory disease, prior chemotherapy courses (>5), or tumor size (>3 cm). There were no RT-related toxicities. Overall survival at 1 year following initial LDRT was 90%, and 1-year progression-free survival following last course was 55%. In summary, LDRT is effective for relapsed, multiply refractory MCL, and may be safely delivered with chemotherapy, to multiple sites, and repeatedly without issue. By treating active sites of disease, LDRT can provide durable local control, help achieve remission, and potentially bridge patients to subsequent novel therapies.