In this work, an efficient topology optimization approach is proposed for a three-dimensional (3D) flexible multibody system (FMBS) undergoing both large overall motion and large deformation. The FMBS of concern is accurately modeled first via the solid element of the absolute nodal coordinate formulation (ANCF), which utilizes both nodal positions and nodal slopes as the generalized coordinates. Furthermore, the analytical formulae of the elastic force vector and the corresponding Jacobian are derived for efficient computation. To deal with the dynamics in the optimization process, the equivalent static load (ESL) method is employed to transform the topology optimization problem of dynamic response into a static one. Besides, the newly developed topology optimization method by moving morphable components (MMC) is used and reevaluated to optimize the 3D FMBS. In the MMC-based framework, a set of morphable structural components serves as the building blocks of optimization and hence greatly reduces the number of design variables. Therefore, the topology optimization approach has a potential to efficiently optimize an FMBS of large scale, especially in 3D cases. Two numerical examples are presented to validate the accuracy of the solid element of ANCF and the efficiency of the proposed optimization methodology, respectively.