Rotatable antenna (RA) enhances wireless coverage through directional gain steering, yet suffers from performance degradation under physical blockages. Intelligent reflecting surface (IRS) establishes reflective paths to bypass obstacles, but suffers from angular mismatch when deployed in the side-lobe region of base station (BS) antennas. To address this issue, we propose a new RA-enabled IRS-assisted multi-user uplink system, in which the BS antennas are capable of flexibly adjusting their 3D orientations to align their boresights with the IRS. We formulate a sum rate maximization problem by jointly optimizing the antenna 3D rotations, receive beamforming and IRS phase shifts. To tackle this non-convex problem, we propose an efficient alternating optimization (AO) algorithm. Specifically, we iteratively update the antenna rotations via projected gradient ascent (PGA), compute the receive beamforming via a closed-form solution, and optimize the IRS phase shifts via fractional programming (FP). Numerical results demonstrate that the proposed system yields significant performance gains over conventional fixed-antenna systems, especially under large angular misalignments.