<p>There is currently no standardized, empirically validated treatment for severe anxious school refusal (ASR) in adolescents. Cognitive-behavioural therapy (CBT) is the most studied intervention but has not been evaluated in severe cases involving total school non-attendance. This multicentre, single-arm, phase II trial using an A’Hern single-stage design - chosen to set an a priori efficacy threshold in the absence of prior trials for severe cases – included adolescents aged 10–16 years with ASR (per Berg’s criteria), at least one primary anxiety disorder diagnosis and total school non-attendance for at least five consecutive days. Participants with neuro-developmental disorders or intellectual disabilities were excluded. An intensive CBT program was delivered in day hospital care four times a week. It included individual and group therapy sessions, school sessions, parental support, and a progressive return-to-school plan. Partial school attendance and therapeutic contact continued weekly until the end of the school year. The primary outcome was ≥ 80% school attendance at 6 months post-intervention, with a predefined minimal efficacy threshold of 30%. Secondary outcomes included anxiety and global functioning. Among 65 participants (mean age 13.3 ± 1.2; 70.8% girls), most (69.2%) had at least three MINI-S-KID anxiety disorders. Median school absence was five weeks and intervention duration ranged from 1.6 to 9.9 months (median 6.8). At 6 months, 53.1% (95% CI: 38.3–67.5) of the 49 with available data reached the 80% attendance threshold. Overall, 96% returned to school, with median attendance of 85% at 6 months and 77% at 12 months. Anxiety scores and global functioning improved post-intervention and across follow-up. This intensive CBT program appears feasible and effective for adolescents with severe ASR. Findings should be confirmed in a randomized controlled trial.</p><p>Registration: Clinicaltrials.gov, NCT04559633, registration date: 2020/09/16.</p>