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Infliximab [IFX] and adalimumab [ADA] are effective in Crohn’s disease [CD] for induction and maintenance therapy. However, high annual rate of discontinuation for loss of response or intolerance may lead to a switch to another anti-tumor necrosis factor agent. Patients with successive failure to IFX and ADA are becoming more frequent. The aim of this study was to assess the efficacy and the tolerance of re-treatment with IFX in CD patients who successively failed IFX and ADA.A total of 61 patients with CD who received and discontinued successively IFX and ADA, and who were re-exposed to IFX, were identified in four French tertiary centers and retrospectively analyzed. Clinical data, follow-up and outcome were abstracted from medical records.Median treatment duration after reintroduction was 16 months, and probability of remaining under IFX was 60% and 51%, respectively, at 12 and 24 months. In all 29 patients discontinued the second IFX treatment due to intolerance , primary non-response , loss of response  or patient’s wish . Remission was achieved in 42% at week 6–8 after IFX re-induction, and was predictive of better long-term response [p = 0.006]. In multivariate analysis, receiving co-immunosuppression in both first and second IFX treatments [p = 0.04] and shorter interval between first and second IFX treatments [p = 0.017] were independently associated with longer duration of second IFX treatment.For CD patients who successively failed IFX and ADA, reintroducing IFX is feasible and often clinically efficient, particularly in patients who received co-immunosuppression during both first and second IFX treatments.