Background: Traditional multi-agent salvage strategies for lymphoma are less effective after failed modern front line therapies. Bendamustine (Treanda, T) has considerable anti-lymphoma activity and a favorable toxicity profile. We hypothesized that bendamustine could replace ifosfamide within the (R)ICE regimen yielding a feasible and effective salvage strategy (TREC). Methods: This multicenter phase I study used a two stage design followed by 2 expansion cohorts for patients with diffuse large B cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). Eligibility included measurable relapsed/refractory lymphoma, ECOG performance status ≤ 2, adequate blood counts and organ function. The primary objective was to define a maximally tolerated dose (MTD) of bendamustine associated with a dose limiting toxicity (DLT) rate of ≤ 25%. Therapy consisted of bendamustine ranging from 60 mg/m2 to 120 mg/m2 daily on days 1 and 2 with standard doses of carboplatin, etoposide, and rituximab (CD20+ disease only) used in the RICE regimen every 21 days for 2 cycles. Results: A total of 46 treated patients with median age of 58 years and median of 1 prior therapy, were enrolled with 3 at the dose escalation cohorts and 43 at the recommended phase 2 dose (RP2D). MTD was not reached. Primary refractory disease or early relapse was seen in 13 (65%) patients with HL (n = 20) and 14 (74%) patients with DLBCL (n = 19). All cycles were successfully given in the outpatient setting. Fourteen patients suffered ≥ grade 3 non-hematologic adverse events but without DLTs. The most common ones were febrile neutropenia (n = 4, 9%) and rash (n = 3, 4%). Per Cheson 2007 criteria overall response rates were 67% with 84% (14 CR, 2 PR) in HL, and 63% (8 CR, 4 PR) in DLBCL. Mobilization of peripheral blood stem cells (PBSC) was successful in all attempts immediately following the treatment with a median collection of 5.9 x 10⁶CD34/kg. To date, 16 of 22 (77%) CR patients underwent transplant. Conclusions: The outpatient administration, manageable toxicity profile, and high response rate in HL and DLBCL of the TREC regimen are encouraging. These data support future evaluation of TREC. Clinical trial information: NCT01165112