To evaluate the effectiveness and safety of secukinumab in patients with a mucosal and articular Behçet's phenotype resistant to conventional and biologic treatment.A multicentre retrospective study was performed on 15 patients with a mucosal and articular phenotype of Behçet's syndrome fulfilling the International Criteria for Behçet's Disease and refractory to treatment with colchicine, disease-modifying antirheumatic drugs and at least one antitumour necrosis factor-α agent. Minimum follow-up was set at 6 months. Six patients with a polyarticular involvement were treated with secukinumab 300 mg/month, while all other cases received secukinumab 150 mg/month. Dose increase from 150 to 300 mg per month and shortening of administration frequency were allowed for poor disease control. Response evaluation was based on the number of oral ulcers in the previous 28 days and Disease Activity Score-28 for articular manifestations.At 3 months of follow-up, nine (66.7%) patients achieved a response (complete or partial), and this proportion further increased to 86.7% at 6 months, 76.9% at 12 months, 90.0% at 18 months and 100.0% after 24 months. Notably, all patients who started with secukinumab 300 mg/month achieved complete response by month 6. Seven (46.7%) patients could achieve a response only after switching to a higher dosage.Our study suggests that secukinumab at a dose of 150 and 300 mg per month is safe and effective for the long-term treatment of patients with Behçet's syndrome with a mucosal and articular phenotype refractory to previous treatments. Notably, secukinumab 300 mg/month resulted in superior complete mucosal and articular responses with no serious or dose-related adverse effects.