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Objectives: To evaluate the efficacy and tolerability of an attenuated immunochemotherapy regimen based on cytarabine, etoposide and dexamethasone plus rituximab (R‐mini‐CYVE) in patients with relapsed or refractory B‐cell non–Hodgkin's lymphoma (NHL). Methods: We included pretreated adult patients with B‐cell NHL who were ineligible for high‐dose immunochemotherapy (HDT). Cytarabine and etoposide were given at four different dose levels, depending on the patient's frailty. Up to 8 cycles were administered. Results: Between 2013 and 2019, 56 patients with diffuse large B‐cell lymphoma (n = 45, 80%) and indolent B‐cell lymphoma (n = 11, 20%) were included. Median age was 75 (range: 36‐88). Nineteen patients (35%) had a performance status ≥2. Patients received a median of 4 cycles of R‐mini‐CYVE. The objective response and the complete response rates were 50% and 33%, respectively. Median progression‐free survival and overall survival times were 5.7 (95% CI: 0.5‐10.9) and 14.7 (95% CI: 3.5‐25.9) months, respectively. Grade ≥3 anaemia, thrombocytopenia and neutropenia occurred in 44%, 55% and 60% of the patients, respectively. The most frequent non‐haematological grade ≥3 adverse events were sepsis (21%), fatigue (13%) and cytarabine‐related neurotoxicity (5%). Conclusion: R‐mini‐CYVE demonstrated a meaningful antitumour efficacy and an acceptable safety profile in patients with relapsed/refractory B‐cell NHL who were ineligible for HDT. [ABSTRACT FROM AUTHOR]